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B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients.

Authors :
Vietsch EE
Latifi D
Verheij M
van der Oost EWA
de Wilde RF
Haen R
van den Boom AL
Koerkamp BG
Doornebosch PG
van Verschuer VMT
Ooms AHAG
Mohammad F
Willemsen M
Aerts JGJV
Krog RT
de Miranda NFCC
van den Bosch TPP
Mueller YM
Katsikis PD
van Eijck CHJ
Source :
Frontiers in immunology [Front Immunol] 2023 Nov 10; Vol. 14, pp. 1230306. Date of Electronic Publication: 2023 Nov 10 (Print Publication: 2023).
Publication Year :
2023

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae , Bifidobacterium animalis , and Adlercreutzia equolifaciens , while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies.<br />Competing Interests: Author AO was employed by the company Pathan BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2023 Vietsch, Latifi, Verheij, van der Oost, de Wilde, Haen, van den Boom, Koerkamp, Doornebosch, van Verschuer, Ooms, Mohammad, Willemsen, Aerts, Krog, de Miranda, van den Bosch, Mueller, Katsikis and van Eijck.)

Details

Language :
English
ISSN :
1664-3224
Volume :
14
Database :
MEDLINE
Journal :
Frontiers in immunology
Publication Type :
Academic Journal
Accession number :
38022530
Full Text :
https://doi.org/10.3389/fimmu.2023.1230306